The overall objective of this proposal is to evaluate antigen specific T cell responses in different clinical forms of leishmaniasis at both cellular and molecular levels. During the course of these studies we will characterize antigen-specific peripheral blood T lymphocyte responses in visceral, cutaneous, and mucosal leishmaniasis. This specific aim will emphasize phenotypic and functional profiles of peripheral blood mononuclear cells responding to whole leishmania lysate or to defined leishmania antigens. Proliferation and cytokine production will be assessed. In particular, we will emphasize differential characterization of T cells bearing alpha-beta or gamma-delta TcR. We will evaluate cellular cytotoxicity responses in different clinical forms of leishmaniasis. In this specific aim, we will define the cell types involved in leishmania specific cytotoxic responses. This will include studies on the role of defined antigens as both inductor and effector signals. Finally, we will phenotypically and functionally characterize the infiltrating lymphocytes in cutaneous lesions produced by L. amazonensis or L. braziliensis infection. We will evaluate different cell populations for cytotoxic products, as cytotoxic effector cells, and as targets following in vitro infection or pulsing with crude or specific antigens. In addition, we will determine whether cytotoxic effector mechanisms such as perforin or TNF are present. These studies will expand our knowledge of specific protective as well as host pathological responses in leishmaniasis.